Fluorinated Coumarin Derivatives as Selective PET Tracer for MAO-B Imaging

Monoamine oxidase-B (MAO-B), predominantly exists on the outer mitochondrial membrane of astrocytes, serves as a crucial biomarker for reactive astrocytes during neuroinflammatory responses and various neurodegenerative diseases. In this study, we synthesized a series of fluorinated coumarin derivatives and evaluated their structure-activity relationship and subtype selectivity for MAO-B. Following this, the preclinical bioevaluation containing <i>in vivo</i> positron emission tomography (PET) imaging and <i>ex vivo</i> autoradiography studies led to the identification of the novel PET tracer, [¹⁸F]<b>8</b>, which demonstrated high affinity for MAO-B (IC₅₀ = 0.59 nM) and appreciable brain pharmacokinetics (SUV_max = 2.15 at 2 min, brain_2min/60min = 7.67) in rats. Furthermore, the radioactivates from [¹⁸F]<b>8</b> in regions of MAO-B expression could be effectively inhibited by Selegiline. All these positive findings supported that [¹⁸F]<b>8</b> is a promising candidate for MAO-B PET imaging, which merits further evaluation.